STUDY OBJECTIVE: We test the null hypothesis that the "1+1" hydromorphone patient-driven protocol is clinically and statistically equivalent in safety and efficacy to that of traditional physician-driven administration of opioids for emergency department (ED) treatment of acute severe pain. METHODS: This was a prospective randomized clinical trial of nonelderly adults presenting to an urban academic ED with acute pain of sufficient severity to warrant intravenous (IV) opioids in the judgment of the attending physician. Patients randomized to the 1+1 hydromorphone patient-driven protocol received 1 mg IV hydromorphone followed by a second 1-mg dose 15 minutes later if the patient responded affirmatively to the question, "Do you want more pain medication?" Patients in the physician-driven group received any IV opioid in the dose chosen by the ED attending physician, with any additional analgesia provided at the discretion of that physician. The primary outcome was the difference in improvement in pain between the 2 groups at 60 minutes, as measured by a validated and reproducible numeric rating scale. Secondary outcomes included incidence of oxygen desaturation, hypoventilation, hypotension, bradycardia, nausea, vomiting, pruritus, and use of naloxone. RESULTS: The mean decrease in numeric rating scale pain scores for the 1+1 hydromorphone patient-driven group was 5.6 versus 4.5 in the physician-driven group. The difference of 1.1 numeric rating scale units (95% confidence interval 0.3 to 1.9) was statistically significant but fell 0.2 numeric rating scale units short of the 1.3 numeric rating scale unit threshold required to attain clinically significant efficacy. Safety profiles were similarly satisfactory in both groups. Ninety-four percent of the 1+1 hydromorphone patient-driven group achieved adequate analgesia (as defined by the patient) within 60 minutes of protocol initiation. CONCLUSION: The 1+1 hydromorphone patient-driven protocol is statistically superior and at least as clinically efficacious and safe as traditional physician-driven treatment of ED patients with acute severe pain. More than 9 of 10 patients randomized to the study protocol achieved satisfactory pain control, as defined by the patient, within an hour or less.